Ganglionic blockade alters behavioral and cerebral metabolic responses to corticotropin releasing factor in the rat

Corticotropin releasing factor (CRF) has potent stimulating effects on behavior and cerebral metabolism. To investigate the role of altered peripheral autonomic function in central actions of CRF, we measured the effects of intracerebroventricular CRF (2 μg) on locomotor activity and regional cerebral metabolic rates for glucose (rCMRglc) in control, saline pretreated rats and in rats pretreated with the ganglionic receptor blocker hexamethonium bromide (HEX) (5 mg/kg). Locomotor activity was assessed in a familial environment with an activity meter. rCMRglc were measured in 74 brain regions with the quantitative autoradiographic [¹⁴C]2-deoxy-D-glucose technique. In control rats, CRF increased the spontaneous locomotor activity and rCMRglc in 14 sensorimotor, limbic, hypothalamic and brainstem regions. HEX pretreatment blunted locomotor activations induced by CRF. While HEX did not affect cerebral metabolic activation by CRF in sensorimotor areas, it reduced metabolic activations in hippocampal and hypothalamic regions and increased metabolic activations in the brainstem reticular formation. These data indicate that CRF increases rCMRglc in the sensorimotor areas by direct CNS activity and in the limbic areas by indirect, autonomically mediated, activity. Autonomic activation also accounts, at least in part, for the motor activating properties of CRF.